Abstract
Embryonic stem cells (ESCs) can differentiate to endothelial progenitor cells and vascular endothelial cells (VECs), but the mechanism is largely unknown. In this study, we synthesized 2 chiral compounds (R-ABO and S-ABO) and identified R-ABO as an effective inducer of ESC differentiation into VECs. Furthermore, we found that R-ABO induced ESC differentiation into VECs via homeobox containing 1 (Hmbox1) that acted upstream of fibroblast growth factor 2 (FGF-2). The data suggest that R-ABO is a novel tool for ESC differentiation into VECs, and Hmbox1 is a key regulator in this differentiation process. These findings provide information on a novel target and a new platform for further investigating the gene control of ESC differentiation to VECs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inducing Agents / pharmacology*
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Animals
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Becaplermin
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Benzoxazines / pharmacology*
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Cell Culture Techniques
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Cell Differentiation / drug effects*
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Cells, Cultured
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Embryonic Stem Cells / drug effects
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Embryonic Stem Cells / physiology*
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Endothelial Cells / cytology
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Endothelial Cells / metabolism*
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Endothelium, Vascular / cytology
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Fibroblast Growth Factor 2 / metabolism
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Gene Expression
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Integrin beta4 / genetics
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Integrin beta4 / metabolism
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Mice
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Mice, 129 Strain
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Neovascularization, Physiologic
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Proto-Oncogene Proteins c-sis / metabolism
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Stereoisomerism
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Transcriptional Activation
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Vascular Endothelial Growth Factor A / metabolism
Substances
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6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine
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Angiogenesis Inducing Agents
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Benzoxazines
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Hmbox1 protein, mouse
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Homeodomain Proteins
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Integrin beta4
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Proto-Oncogene Proteins c-sis
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Vascular Endothelial Growth Factor A
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vascular endothelial growth factor A, mouse
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Fibroblast Growth Factor 2
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Becaplermin